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Computer-Based Method IDs Alzheimer's Protein Structures

FRIDAY Aug. 22, 2008 -- A new method of identifying protein structures related to Alzheimer's disease has been developed by researchers at the Massachusetts Institute of Technology.

The research team says its computer-based technique could help in the development of drugs that could prevent the formation of such structures.

Alzheimer's disease is characterized by two kinds of proteins (amyloid and tau) that accumulate in the brain. In a study published in the Aug. 22 issue of PLoS Computational Biology, the MIT team focused on tau.

Most proteins have similar structures, so "you can measure the lengths of individual molecules, and the average will be a pretty good description of any one," team leader Dr. Collin M. Stultz, an associate professor of biomedical engineering, explained in an MIT news release.

But tau molecules "are all over the place -- they're so diverse that it's difficult to get one measurement that describes all of the possible structures," Stultz said. This makes it a challenge to detect specific tau structures associated with Alzheimer's.

The MIT team developed a method called Energy-minima Mapping and Weighting (EMW) and "generated lots and lots of structures for both normal tau and a mutant form" associated with an increased risk for Alzheimer's disease.

Further analysis revealed that one structure was more common in the mutant form of tau and therefore likely to play a role in the development of Alzheimer's. That structure could become a target for new drug development, Stultz said.

The study looked at one mutant form of tau associated with Alzheimer's, but there are several others. Stultz said he hopes to use EMW to create "a list of all types of suspect conformations for known tau mutants. Then, from that list, we can design drugs for each."

Posted: August 2008


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